We wish to determine whether natural electrical fields are a significant component in directing the cell growth, differentiation and movement that underlie vertebrate regeneration and wound healing. Our approach to regeneration will be to determine whether inhibition, reversal or shunting of natural limb stump currents by various means will inhibit regeneration of newt and axolotl limbs. These means will include battery imposed countercurrents, media that by virtue of specific ion deficiencies or specific inhibitors of ion channels inhibit these currents, as well as implanted shunts that redirect those currents from their natural targets. It is anticipated that these studies will also lead to insights into the mode of action of these electrical fields. In studing the role of natural electrical fields in wound healing, we will determine the follwing: The size and ionic basis of the currents that presumably leave epidermal wounds in larval amphibians; which epithelial layer drives these currents; and the pattern, direction and magnitude of the fields generated by these currents within the skin. (We will be guided in this inquiry by the hypothesis that the main pertinent fields lie along the narrow space between the two epithelial layers that make up the epidermis of larval amphibia.) We then will see whether enhancement, inhibition or reversal of these fields will speed, slow, or even reverse epidermal wound closure. Two important techniques to be used are: (1) A modification of Jaffe & Nuccitelli's vibrating probe for measuring the density and pattern of electrical currents leaving and entering skin wounds. (2) Woodruff and Telfer's method for detecting (and ultimately measuring) electrical fields. This method involves monitoring the movement of both negatively and positively charged fluorescent-labeled macromolecules in the extracellular spaces within the skin near the wound.